iPSC-Derived Epithelial, Mesenchymal, Endothelial, and Immune Cell Co-Culture to Model Airway Barrier Integrity in Lung Health and Disease.

Human lung tissue is composed of an interconnected network of epithelium, mesenchyme, endothelium, and immune cells from the upper airway of the nasopharynx to the smallest alveolar sac. Interactions between these cells are crucial in lung development and disease, acting as a barrier against harmful chemicals and pathogens. Current in vitro co-culture models utilize immortalized cell lines with different biological backgrounds, which may not accurately represent the cellular milieu or interactions of the lung.

The impact of breastfeeding on the preterm infant's microbiome and metabolome: a pilot study.

Background: Human milk is unquestionably beneficial for preterm infants. We investigated how the transition from tube to oral/breastfeeding impacts the preterm infants' oral and gut microbiome and metabolome.

Methods: We analyzed stool, saliva, and milk samples collected from a cohort of preterm infants enrolled in the MAP Study, a prospective observational trial.

A therapy for suppressing canonical and noncanonical SARS-CoV-2 viral entry and an intrinsic intrapulmonary inflammatory response.

The prevalence of "long COVID" is just one of the conundrums highlighting how little we know about the lung's response to viral infection, particularly to syndromecoronavirus-2 (SARS-CoV-2), for which the lung is the point of entry. We used an in vitro human lung system to enable a prospective, unbiased, sequential single-cell level analysis of pulmonary cell responses to infection by multiple SARS-CoV-2 strains. Starting with human induced pluripotent stem cells and emulating lung organogenesis, we generated and infected three-dimensional, multi-cell-type-containing lung organoids (LOs) and gained several unexpected insights.

Impact of climate change on paediatric respiratory health: pollutants and aeroallergens.

Paediatric populations are particularly vulnerable to respiratory diseases caused and exacerbated by aeroallergens, pollutants and infectious agents. Worsening climate change is expected to increase the prevalence of pollutants and aeroallergens while amplifying disease severity and causing disproportionate effects in under-resourced areas. The purpose of this narrative review is to summarise the role of anthropogenic climate change in the literature examining the future impact of aeroallergens, pollutants and infectious agents on paediatric respiratory diseases with a focus on equitable disease mitigation.

EGFR-Driven Lung Adenocarcinomas Co-opt Alveolar Macrophage Metabolism and Function to Support EGFR Signaling and Growth.

Unlabelled: The limited efficacy of currently approved immunotherapies in EGFR-driven lung adenocarcinoma (LUAD) underscores the need to better understand alternative mechanisms governing local immunosuppression to fuel novel therapies. Elevated surfactant and GM-CSF secretion from the transformed epithelium induces tumor-associated alveolar macrophage (TA-AM) proliferation, which supports tumor growth by rewiring inflammatory functions and lipid metabolism. TA-AM properties are driven by increased GM-CSF-PPARγ signaling and inhibition of airway GM-CSF or PPARγ in TA-AMs suppresses cholesterol efflux to tumor cells, which impairs EGFR phosphorylation and restrains LUAD progression.

EGFR-driven lung adenocarcinomas coopt alveolar macrophage metabolism and function to support EGFR signaling and growth.

The limited efficacy of currently approved immunotherapies in EGFR-driven lung adenocarcinoma (LUAD) underscores the need to better understand alternative mechanisms governing local immunosuppression to fuel novel therapies. Elevated surfactant and GM-CSF secretion from the transformed epithelium induces tumor-associated alveolar macrophage (TA-AM) proliferation which supports tumor growth by rewiring inflammatory functions and lipid metabolism. TA-AM properties are driven by increased GM-CSF-PPARγ signaling and inhibition of airway GM-CSF or PPARγ in TA-AMs suppresses cholesterol efflux to tumor cells, which impairs EGFR phosphorylation and restrains LUAD progression.

The re-emerging role of linoleic acid in paediatric asthma.

Asthma is the most common chronic disease within the paediatric population. Although it is multifactorial, its onset may be linked to early-life exposures with subsequent impact on immune system development. Microbial and dietary metabolic products have been implicated in the development and exacerbation of paediatric asthma.

A neonatal case of vascular ring with Alagille syndrome.

A female infant, born at 37 week 5 days to a mother via induced vaginal delivery for preeclampsia, was prenatally diagnosed with a right aortic arch with vascular ring. On the third day of life, the infant exhibited a bronze-gray coloration, and a direct bilirubin of 1.7 mg/dL was detected.

Leveraging the placenta to advance neonatal care.

The impact of placental dysfunction and placental injury on the fetus and newborn infant has become a topic of growing interest in neonatal disease research. However, the use of placental pathology in directing or influencing neonatal clinical management continues to be limited for a wide range of reasons, some of which are historical and thus easily overcome today. In this review, we summarize the most recent literature linking placental function to neonatal outcomes, focusing on clinical placental pathology findings and the most common neonatal diagnoses that have been associated with placental dysfunction.

EGFR lung adenocarcinomas coopt alveolar macrophage metabolism and function to support EGFR signaling and growth.

The limited efficacy of currently approved immunotherapies in EGFR-mutant lung adenocarcinoma (LUAD) underscores the need to better understand mechanisms governing local immunosuppression. Elevated surfactant and GM-CSF secretion from the transformed epithelium induces tumor-associated alveolar macrophages (TA-AM) to proliferate and support tumor growth by rewiring inflammatory functions and lipid metabolism. TA-AM properties are driven by increased GM-CSF-PPARγ signaling and inhibition of airway GM-CSF or PPARγ in TA-AMs suppresses cholesterol efflux to tumor cells, which impairs EGFR phosphorylation and restrains LUAD progression.

Mediating Role of Fine Particles Abatement on Pediatric Respiratory Health During COVID-19 Stay-at-Home Order in San Diego County, California.

Lower respiratory tract infections disproportionately affect children and are one of the main causes of hospital referral and admission. COVID-19 stay-at-home orders in early 2020 led to substantial reductions in hospital admissions, but the specific contribution of changes in air quality through this natural experiment has not been examined. Capitalizing on the timing of the stay-at-home order, we quantified the specific contribution of fine-scale changes in PM concentrations to reduced respiratory emergency department (ED) visits in the pediatric population of San Diego County, California.

Allergen Content and Protease Activity in Milk Feeds from Mothers of Preterm Infants.

There is little information regarding the allergen content of milk feeds in the preterm population. Previous studies have not performed a broad analysis of the allergenic peptide content and protease activity of milk feeds in this population. To evaluate feasibility, we initially performed mass spectrometry on 4 human milk (HM) samples (2 term and 2 preterm) from the Mommy's Milk Human Milk Biorepository (HMB) and analyzed the results against the University of Nebraska FASTA database and UniProt for a total of 2,211 protein sequences.

Dose-dependent association between inhaled corticosteroid use and risk of obesity and metabolic syndrome in asthma.

Inhaled corticosteroids (ICS) are widely prescribed medications. Some studies have reported that ICS may suppress the hypothalamic-pituitary-adrenal axis and induce systemic effects. To explore the possibility of a dose-dependent association between the long-term use of ICS and the risk of obesity and other markers of metabolic syndrome.

Patterns of allergenic food introduction in Los Angeles inner-city children.

Background: Early introduction of allergenic foods is recommended to reduce the risk of developing food allergies, but it is unclear whether recommendations are being followed.

Objective: We examine patterns of allergenic food introduction in inner-city children enrolled in an academic pediatric practice in the greater Los Angeles area.

Methods: This was a prospective study with patients ages 12 to 24 months recruited from the pediatrics continuity clinic at an inner-city tertiary medical center in the greater Los Angeles area.

Conformational flexibility in neutralization of SARS-CoV-2 by naturally elicited anti-SARS-CoV-2 antibodies.

As new variants of SARS-CoV-2 continue to emerge, it is important to assess the cross-neutralizing capabilities of antibodies naturally elicited during wild type SARS-CoV-2 infection. In the present study, we evaluate the activity of nine anti-SARS-CoV-2 monoclonal antibodies (mAbs), previously isolated from convalescent donors infected with the Wuhan-Hu-1 strain, against the SARS-CoV-2 variants of concern (VOC) Alpha, Beta, Gamma, Delta and Omicron. By testing an array of mutated spike receptor binding domain (RBD) proteins, cell-expressed spike proteins from VOCs, and neutralization of SARS-CoV-2 VOCs as pseudoviruses, or as the authentic viruses in culture, we show that mAbs directed against the ACE2 binding site (ACE2bs) are more sensitive to viral evolution compared to anti-RBD non-ACE2bs mAbs, two of which retain their potency against all VOCs tested.

A Perspective on Pediatric Respiratory Outcomes During California Wildfires Due to Smoke and PM Exposure.

As wildfires increase in prevalence and intensity across California and globally, it is anticipated that more children will be exposed to wildfire smoke, and thus face associated adverse health outcomes. Here, we provide a concise summary of the respiratory effects of California's wildfires on pediatric healthcare utilization, examine global examples of wildfire smoke exposure within the pediatric population and associated physiological effects, and assess the efficacy of metrics used to measure and communicate air quality during wildfires within the United States and elsewhere.

Structure-selected RBM immunogens prime polyclonal memory responses that neutralize SARS-CoV-2 variants of concern.

Successful control of the COVID-19 pandemic depends on vaccines that prevent transmission. The full-length Spike protein is highly immunogenic but the majority of antibodies do not target the virus: ACE2 interface. In an effort to affect the quality of the antibody response focusing it to the receptor-binding motif (RBM) we generated a series of conformationally-constrained immunogens by inserting solvent-exposed RBM amino acid residues into hypervariable loops of an immunoglobulin molecule.

Immune-Mediated Neonatal Thrombocytopenia.

Immune-mediated thrombocytopenia in neonates is caused by the transplacental passage of maternally derived antiplatelet antibodies. The 2 most common causes include neonatal alloimmune thrombocytopenia, which leads to significant thrombocytopenia and risk of intracranial hemorrhage, and autoimmune thrombocytopenia, which is generally less severe. No specific guidelines for prenatal management exist for either disease; however, intravenous immune globulin treatments and systemic steroids for women with at-risk pregnancies can be useful in both diseases.

The impact of maternal asthma on the preterm infants' gut metabolome and microbiome (MAP study).

Preterm infants are at a greater risk for the development of asthma and atopic disease, which can lead to lifelong negative health consequences. This may be due, in part, to alterations that occur in the gut microbiome and metabolome during their stay in the Neonatal Intensive Care Unit (NICU). To explore the differential roles of family history (i.

Discovery and functional interrogation of SARS-CoV-2 protein-RNA interactions.

The COVID-19 pandemic is caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). The betacoronvirus has a positive sense RNA genome which encodes for several RNA binding proteins. Here, we use enhanced crosslinking and immunoprecipitation to investigate SARS-CoV-2 protein interactions with viral and host RNAs in authentic virus-infected cells.

Discovery and functional interrogation of SARS-CoV-2 protein-RNA interactions.

The COVID-19 pandemic is caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). The betacoronvirus has a positive sense RNA genome which encodes for several RNA binding proteins. Here, we use enhanced crosslinking and immunoprecipitation to investigate SARS-CoV-2 protein interactions with viral and host RNAs in authentic virus-infected cells.